Coriolus (Trametes) versicolor Cov-1. (L. ex Fr.) Quel.

Its common name in Chinese is Yun-zhi , it means "Cloud mushroom" also known as turkey tail.

After comparison of more than 200 types of mushrooms. Coriolus was  found to have the least cumulative toxicity; best balancing in nutrition, medicinal values and best immune-modulation;  was selected as the most suitable supplement  for long term cancer co-treatment.  The world's top selling all-natural nutritional product used by cancer patients.
	Original Coriolus PSP, ( more than simple mushroom extract ).   now it is called  PSP--Classic
The mushroom has historically attracted attention as a health-oriented food not only in China and Japan but also worldwide. The anti-tumor effect of various kinds of mushroom components has been noted during the last decade. The most potent strain examined was Coriolus versicolor in which PSK was extracted from Basidiomycetes reported from Japan in 1965 and PSP from strain Cov-1 (Yun zhi) reported from China in 1984. Many experimental studies and clinical investigations of PSK and PSP in relation to their anti-tumor effect and especially for their potential use in cancer immunotherapy have been reported. It was found that the anti-tumor effect of PSP was more potent than that of PSK. Mable M.P. Yang, Zhinan Chen, John S.L. Kwok . The Anti-tumor effect of Small Polypeptide from Coriolus versicolor (SPCV). American Journal of Chinese Medicine, Vol. XX, Nos. 3-4, pp. 221-232
In 1965 Japanese scientists first extracted Yun-zhi as  PSK, soon it was approved to be used for a number of cancers, and is covered by the Japanese health care plan.  Now it is one of the most used cancer co-therapeutic substance in Japan.
PSK exhibits a marked antineoplastic effect against both syngeneic and allogeneic tumors of experimental animals when administered intraperitoneally or orally. There is strong evidence that in a tumor model with tumor-specific transplantation antigen (TSTA), that PSK's antitumor effect is through T-cell mediated immunity. Tsukagoshi, S., Hashimoto, Y., Fujii, G., Kobayashi, H., Nomoto, K. and Orita, K., Cancer treatment Reviews (1984)11, 131-155
The protein-bound polysaccharide that contains Alpha-1,4;  Beta 1,3 glycosidic and beta 1,6 glycosidic bond. The polysaccharopeptide of PSP is not an ordinary beta glucan. The determination of PSP with gas chromatography and HPLC has proved that in addition to glucose, PSP contains 5 other monosaccharides, there are mannose, xylose, galactose, rhamnose and arabinose. When PSP is analyzed with gas chromatography and mass spectroscopy according to Hakomori method, PSP is found to contain a large number of 2,4,6 trimethyl glucose. It reveals that PSP contains 1,3 glycosidic bond. The infrared spectrum of PSP shows that there is an obvious absorption at 8.93 cm-1 of the characteristic vibration zone. In addition when PSP is analyzed with nuclear magnetic resonance spectroscopy, there are strong resonance signals at 5.4 PPM of the hydrogen spectrum and 90.35 PPM of carbon spectrum. All these studies prove that in PSP 1,3 glycosidic bond there exists beta connection. It is known that beta 1,3 glucan is the activator of the anti-cancerous immune system of the human body. Sephadex gel chromatograph, DEAE-cellulose column chromatography and HPLC reveal that the polysaccharide and peptide of PSP are closely bound and not separated. Where there is polysaccharide there is polypeptide. It shows that PSP polysaccharide is connected with all small molecular protein (polypeptide). A number of literatures works have proved that only those fungal polysaccharide that are bound with protein can produce anti-tumor effect after oral administration to patients.
PSP is an anticarcinogen and immunological regulator identified as a polysaccharide peptide. It is composed of five monosaccharides: galactose, glucose, mannose, arabinose and xylose. The amino acids most frequently found are aspartic and glutamic. Molecular weight about 1x105 Dalton. Q.Y. Yang, S.C. Yong and X.T. Yang , The Physio-Chemical Characteristics of the Polysaccharide-peptide (PSP) of Coriolus versicolor (Yun zhi)
American National Cancer Research Center has put PSP on record as a fungous anticancerous substance. Applied Microbiology, Vol. 34, p. 183-264. 1989 Canadian Dr. Terry Willard received distinguished Achievement Award in June 1993, at U.S. Chinese Medical Association and National Society of Oriental Medicine Conference, reported that the pharmacological effect of PSP is higher than PSK, Terry Willard, Reishi Mushroom. p. 134. Sylvan Press Co. 1992

Experimental studies of PSK for the prevention of carcinogenesis

Tsukagoshi, S. et al., Cancer treatment Reviews (1984)11, 131-155

PSK extracted from Coriolus versicolor strain CM-101, PSP also extracted from Coriolus versicolor but strain Cov-1.

The inhibitory effect of SPCV, PSP and PSK on leukemia cell

Human Leukemia-60 cells were cultured with different concentration of drugs for 48 Hrs. Cytotoxic activities of the drugs were assessed by ³H-TdR incorporation for 24 hrs. Yang et al., The Anti-tumor Effect of a Small Polypeptide from Coriolus versicolor (SPCV), American Journal of Chinese Medicine, Vol. XX, Nos. 3-4, pp. 221-232

PSP has been proved to be effective against tumor both in animal experiments and in clinical patients. Previous results suggested that the antitumor effects of PSP were related to the potentiation of immunological responses, especially T-cell mediated immune responses of tumor-bearing hosts. Xiao-yu Li, Jia-fang Wang et al, "Immunomodulating Actions of PSP Chinese Academy of Sciences, Shanghai Institute of Materia Medica, Chinese Academy of Science."

Macrophages play an important role in the host defense system by ingestion of ingestion of infectious micro-organisms followed by digestion with lysosomal enzymes. Macrophages can also be activated by lymphokines, endotoxin, and various cell mediators and regulators to kill tumor cells mediators and regulators to kill tumor cells by producing tumor necrosis factor, oxygen radicals, and reactive nitrogen intermediates. When mice were pretreated with PSP, the production of these molecules by macrophages was greatly enhanced, indicating that PSP is an immunomodulatory rather than a direct cytotoxic substance on the tumor cells tested. W.K. Liu, T.B. Ng, S.F. Sze and K.W. Tsui, Immunopharmacology, 26 (1993) 139-146

Recent experiments suggest three possible mechanisms by which these PSP might act: (1) Potentiating of T-cell mediated cytotoxicity, which killed more number of target-tumor cells. (2) Definite concentration of PSP produced direct cytotoxic activity in vitro. (3) Induction of tumorcidal macrophages killed more cancer cells. Jin-Xu Zhou, Xin-LI- Shen, Zu-ming Shen, Xizo-yu Li . "Antitumor effect of PSP of Coriolus versicolor and it mechanics."

It has been indicated that PSP has similar properties to those of PSK produced by Sankyo Ltd. in Japan. Both PSP and PSK are considered to have antitumor effects by the United States National Cancer Institute (Jong and Donovick 1989) and are commercially available. Experimental and clinical studies have shown that PSP is effective in inhibiting the proliferation of P388 leukemia cells, Ehrlich ascites and some human tumor cells in vitro, and solid tumor growth in vivo as well as in stimulating both humoral and cellular immune responses. Also PSP is of notable value in maintaining or even raising white blood cell counts in mice treated with cyclophosphamide (CPA) and in breast cancer patients who are given three cycles of chemotherapy including the use of cyclophosphamide. The results demonstrated that PSP possessed immunopotentiating effect, being effective in restoring cyclophosphamide (CPA) induced immunosuppression such as depressed lymphocyte proliferation, Natural Killer cell function, production of white blood cell and the growth of spleen and thymus in rats as well as in increasing both IgG and IL-2. Zhong Ming Qing, Mei Feng Xu and Pak Lai Tang, . Polysaccharide Peptide (PSP) Restores Immunosuppression Induced by Cyclophosphamide in Rats, American Journal of Chinese Medicine Vol. XXV, No. 1, p.p. 27-35

In China, under the supervision of the Department of Health of Shanghai, PSP was given to 485 patients with cancers of esophagus, stomach, and primary lung cancer. The results have shown that PSP has the function of improving the following symptoms of cancer patients after chemotherapy and radiotherapy, such as deficiency of vital energy and insufficiency of body fluid with irritability, thirst, constipation, etc. besides it has protective and improving effects on immunological functions as well as on the blood picture. "Phase II Clinical Trial for PSP Capsules" Health Care, Hong Kong, 1993 p. 10-12

Studies include the clinical trial on 485 cases of cancer patients who have used PSP for the treatment of cancer alone or in combination with chemotherapy and radiotherapy. The results of these studies have consistently shown increased survival rates and improved quality of life without toxic side effects. The total effective rate is 82.96%. "Phase II Clinical Trial for PSP Capsules" Health Care, Hong Kong, 1993 p. 10-12

Comparison of various types of Coriolus versicolor products on the market

The mouse macrophage-like cell line, J774.1, spontaneously released differentiation-inducing factors. When these cells were treated with a protein-bound polysaccharide, PSK, significantly higher amounts of differentiation-inducing activity were accumulated in the culture supernatant. PSK directly stimulated human myelogenous leukemice cell differentiation induced by J774.1 conditioned medium or by tumor necrosis factor. Among four subfractions of PSK, only the highest molecular weight fraction (MW greater than 200 KD) exerted such a stimulating effect. Sakagami, H., Ikeda, M., Konno, K., Stimulation of tumor necrosis factor-induced human myelogenous leukemic cell differentiation by high molecular weight PSK subfraction., First Department of Biochemistry, School of Medicine, Showa University, Tokyo, Japan.

The antitutor effect of PSK, a Coriolus preparation, was analyzed with the double grafted tumor system in which BALB/c mice received intradermal inoculations of syngeneic Meth-A fibrosarcoma in the right (primary tumor, 10(6) cells) and left (distant tumor, 2 x 10(5) cells) flands. Intratumoral administration of PSK significantly inhibited the growth of not only the right but also the left tumor. PSK also inhibited the growth of a methylcholanthrene-induced fibrosarcoma BAMC-1, and a methylurethane-induced adenocarcinoma Colon 26 in the double grafted tumor system of syngeneic BALB/c mice. However, when the left distant tumor was different from he right Meth-A tumor, the intratumoral administration of PSK in the right tumor was unable to inhibit the growth of the left BAMC-1 or RL male-1 tumor. The PSK-induced immunity, therefore, is tumor-specific and T-lymphocytes may play an important role in antitumor memory function. On the other hand, the antitumore effect of PSK was enhanced by previous intravenous administration of an anti-metabolite, 5-fluorouracil.Kariya, Y., Okamoto, N., Fujimoto, T., Inoue, N., Kihara, T., Sugie, K., Yagita, M., Kanzaki, H., Mori, T., Uchida, A., Lysis of fresh human tumor cells by autologous peripheral blood lymphocytes and tumor-infiltrating lymphocytes activated by PSK. In: Jpn J. Cancer REs. (1991 Sep) 82(9):1044-50

The isolation and characterization of an immunomodulatory and anti-tumor polysaccharide preparation from Flammulina velutipes. , Alkaline-soluble antitumor polysaccharide was prepared from the cell wall of the mushroom Flammulina velutipes. The backbones of the polysaccharide is mainly composed of beta-(1-->3)-D-linked glucose and its molecular weight was estimated to be about 200 kD. The polysaccharide was found to be non-toxic by brine shrimp assay. When injected into mice intraperitoneally, the polysaccharide triggered proliferation of splenic lymphocytes and also vascular dilation and hemorrhage (VDH) response. The polysaccharide exhibited potent anti-tumor activity against sarcoma SC-180 in vivo but not in vitro.,Leung MY; Fung KP; Choy YM, Department of Biochemistry, Chinese University of Hong Kong, Shatin, N.T., Hong Kong., Immunopharmacology, 35(3):255-63 1997 Jan

Oral administration of PSK can improve the impaired anti-tumor CD4+ T-cell response in gut-associated lymphoid tissue (GALT) of specific-pathogen-free mice. We investigated both the effect and the mechanism of oral (p.o.) administration of PSK, a protein-bound polysaccharide derived from Basidiomycetes, on the anti-tumor T-cell response in gut-associated lymphoid tissue (GALT). The p.o. administration of PSK significantly suppressed the growth of colon 26 carcinoma (C-26) inoculated into the subserosal space of the cecum (i.c.), and augmented the tumor-neutralizing activity of the draining mesenteric lymph node (LN) cells. PSK treatment also significantly decreased the levels of immunosuppressive factors such as plasma transforming growth factor (TGF)-beta in the i.c. C-26-inoculated mice. We also evaluated the improving effect of PSK on the anti-tumor T-cell response in GALT by utilizing B7-transfected P815 mastocytoma (B7/P815). The PSK treatment promoted the rejection of i.c.-inoculated B7/P815 and restored the CD4+ T-cell-dependent proliferative response of the draining mesenteric LN cells against in vitro restimulation. Furthermore, the treatment also decreased the TGF-beta production but increased the IFN-gamma production of these cells. The p.o. administration of PSK, however, showed no effect in the CD8+ T-cell-dependent cytolytic activity of the draining mesenteric LN cells after in vitro re-stimulation. Overall, these results indicate that the p.o. administration of PSK can improve the impaired anti-tumor CD4+ T-cell response in GALT, mainly through a suppression of TGF-beta production and a restoration of IFN-gamma production. Harada M; Matsunaga K; Oguchi Y; Iijima H; Tamada K; Abe K; Takenoyama M; Ito O; Kimura G; Nomoto K, Department of Virology, Kyushu University, Fukuoka, Japan., harada@bioreg.kyushu-u.ac.jo , Int J Cancer, 70(3):362-72 1997 Jan 27

ICRF-187 rescue in etoposide treatment in vivo. A model targeting high-dose topoisomerase II poisons to CNS tumors. The catalytic cycle of topoisomerase II is the target of some of the most successful antitumor agents used today, e.g. etoposide (VP-16), in the treatment of testicular cancer and small-cell lung cancer. The cell kill mediated by topoisomerase II poisons can be antagonized by distinct drug types. Thus, we have demonstrated etoposide antagonism with the type-II anthracycline aclarubicin, the antimalarial drug chloroquine, and the cardioprotective agent ICRF-187. In other setups, combinations of agonist and antagonists have led to high-dose regimens for counteracting drug resistance. Thus, the exploitation of folinic acid rescue for methotrexate toxicity and the use of mesna to protect against cyclophosphamide toxicity have enabled the use of high-dose methotrexate and cyclophosphamide protocols. Using a similar approach, we have studied possible ways to apply antagonists to topoisomerase II poisons. NDF1-hybrid female mice were treated with the various drugs and drug combinations. Lethality (LD10 and LD50 values) was computed by use of the maximum-likelihood method, and the antitumor effect of the drugs was compared in mice inoculated i.p. with either L1210 cells or Ehrlich ascites tumor cells. In addition, the compounds were tested on L1210 cells inoculated intracranially. The toxicity of the various drugs was evaluated by weight and leukocyte counts. ICRF-187 rescues healthy mice from lethal doses of topoisomerase II poisons. In mice the ICRF-187 LD10 was 500 mg/kg. Within a wide non-toxic dose range (50-250 mg/kg) of ICRF-187 we found protection against m-AMSA and etoposide lethality. Thus, the LD10 of etoposide increased from 34 mg/kg for the single agent to 122 mg/kg for its combination with ICRF-187, corresponding to a 3.6-fold etoposide dose escalation. In contrast, ICRF-187 did not protect against lethal doses of the non-topoisomerase II-directed drug paclitaxel. We further investigated the anti-tumor effect of equitoxic schedules in mice inoculated i.p. with L1210 or Ehrlich ascites tumor cells. The L1210-bearing mice appeared to obtain a larger increase in life span from the etoposide and ICRF-187 combination as compared with etoposide alone, whereas this was not the case in mice inoculated with Ehrlich ascites tumor cells. As the hydrophilic ICRF-187 is not expected to cross the blood-brain barrier, in contrast to the lipophilic etoposide, we investigated the effect of the drug combination in mice inoculated intracranially with L1210 cells. We obtained a significant increase in life span in mice treated with ICRF-187 + etoposide as compared with mice treated with an equitoxic dose of etoposide alone. Thus, there appear to be potential routes by which one can benefit from this antagonism. ICRF-187 is a powerful nontoxic protector against the lethality of the topoisomerase II-directed drugs etoposide and m-AMSA in vivo. A brain tumor model demonstrates the superiority of high-dose etoposide treatment with ICRF-187 protection as compared with etoposide treatment alone. This implies that tumors in the brain can be reached by cytotoxic drug doses and that normal tissues can be protected due to differences in drug transport across the blood-brain barrier. ICRF-187 is therefore a promising lead compound for the development of schedules using high-dose topoisomerase II poisons in the treatment of brain tumors and metastases., Holm B; Jensen PB; Sehested M ,Department of Oncology, Rigshospitalet, Copenhagen, Denmark. ,Cancer Chemother Pharmacol, 38(3):203-9 1996

Protein bound polysaccharide PSK abrogates more efficiently experimental metastases derived from H-2 negative than from H-2 positive fibrosarcoma tumor clones. We studied the effect of protein-bound polysaccharide PSK on metastatic colonization of BALB/c mice after intravenous injections of different syngeneic murine H-2 positive and H-2 negative tumor clones. The tumor lines used were different clones from chemically induced fibrosarcomas (GR9.B9, an H-2 negative clone from GR9 tumor, and B7.1.B4, an H-2 positive clone from B7.1 tumor). These clones were selected because of their different sensitivity to NK cytotoxicity, which was related to MHC class I expression. Pretreatment of mice with PSK inhibited metastatic colonization derived from B9 H-2 negative tumor cells. In contrast, lung colonization of PSK treated mice injected with B7.1.B4 H-2 positive tumor cells was higher, and differences in the number of colonies between untreated and PSK treated mice were small. In several experiments the effect of PSK was attenuated to a greater degree when high numbers of cells were injected. Abrogation of NK cells with anti-asialo GM1 serum significantly increased (in all tumors and at different cell doses) the number of metastatic colonies in comparison with untreated mice injected with tumors, regardless of the cell dose used. These results clearly suggest that NK cell activation in vivo by the protein bound polysaccharide PSK abrogates metastasis formation in mice. Abrogation was dependent on the H-2 phenotype even when pretreatment consisted of a single dose of PSK. This effect, related to the NK sensitivity of the tumor target, can be used to predict the effect of PSK in vivo. Algarra I; Collado A; Garrido F , Departamento de Analisis Clinicos e Immunologia, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Spain. ,J Exp Clin Cancer Res, 16(4):373-80 1997 Dec

The role of neutrophils as cytotoxic cells in lung metastasis: suppression of tumor cell metastasis by a biological response modifier (PSK). We aimed to determine the role of neutrophils and the usefulness of a protein-bound polysaccharide (PSK) in the suppression of tumor cell metastasis in the lung in vivo. Circulating neutrophils collected frm tumor-bearing animals (Line-10 hepatocarcinoma) induced a marked decrease in the size and number of metastatic foci in the lung. Although pulmonary macrophages (PAMs), lymphocyte and eosinophil in bronchoalveolar lavage (BAL) fluid increased following tumor cell inoculation, in addition to these findings we found that PSK caused an increase in BAL neutrophil levels causing increased of target cell toxicity and a marked decrease in the size and the number of lung metastatic foci. Superoxide anion generation of blood neutrophils collected from PSK-treated animals with metastasis showed forward acceleration. The presence of neutrophil chemotactic factors was confirmed in the BAL fluid of PSK-treated animals with metastasis, but not leukotriene B4. The results suggest that modulation of the tumor cell microenvironment by activation of neutrophils may prove to be an additional modality in treatment strategy by combining PSK as a biological response modifier with conventional therapies for lung metastasis. Ishihara Y; Fujii T; Iijima H; Saito K; Matsunaga K ,Department of Hygiene and Public Health (I), Tokyo Women's Medical College, Japan. ishihara@reserch.twmc.ac.jp ,In Vivo, 12(2):175-82 1998 Mar-Apr.

Immunotherapy for esophageal cancer. A randomized trial in combination with radiotherapy and radiochemotherapy. Cooperative Study Group for Esophageal Cancer in Japan., We investigated the effect of multimodal therapy in 187 patients with esophageal cancer. All patients were followed up over a period of 5 years. Among the 187 patients, 174 (93.1%) eligible patients with biopsy-proved esophageal squamous cell carcinoma underwent esophagectomy and were randomly assigned to receive radiotherapy (RT) with or without protein-bound polysaccharide (PSK), or RT plus chemotherapy (CT) with or without PSK. The 5-year survival rates of patients with RT, RT+PSK, RT+CT and RT+CT+PSK were 40.0%, 42.3%, 29.1% and 37.2%, respectively. There was a tendency for longer survival on PSK, but statistical significance was not reached (RT+CT group versus RT+CT+PSK group: log-rank and generalized Wilcoxon tests, P = .1930, P = .1034). However, Cox multivariate regression analysis indicated that postoperative therapy with or without PSK was the most significant prognostic factor for patients receiving RT+CT and for the eligible patients. These results indicate that PSK may have a beneficial effect on esophageal carcinoma when given in combination with CT+RT. ,Ogoshi K; Satou H; Isono K; Mitomi T; Endoh M; Sugita M ,Department of Surgery II, Tokai University, Kanagawa, Japan. ,Am J Clin Oncol, 18(3):216-22 1995 Jun

Immunochemotherapies versus chemotherapy as adjuvant treatment after curative resection of operable breast cancer. In our previous study, oral adjuvant combination chemotherapy of 5-fluorouracil, cyclophosphamide, mitomycin C, and predonisolone (FEMP) after curative resection of operable breast cancer with vascular invasion in the tumor and/or in the metastatic lymph node was found to be more effective than one course of mitomycin C or cyclic course of mitomycin C. In the present study, we have assessed the efficacy of protein-bound polysaccharide (PSK) or levamisole (LMS) in addition to FEMP. Between January 1980 and December 1990, 227 operable breast cancer patients with vascular invasion in the tumor and/or in the metastatic lymph node were randomized into FEMP, FEMP + LMS, or FEMP + PSK. The risk ratio was lower in the FEMP + PSK group compared to the FEMP group. In disease-free survival or overall survival, there was no significant difference between the three groups, however, the survival curve of the FEMP + PSK group tended to be better than that of the FEMP group(logrank, P = 0.0706; generalized Wilcoxon, P = 0.0739). Side effects were observed at a low incidence, but they were mild and tolerable. Immunochemotherapy using PSK improved the prognosis of patients with operable breast cancer with vascular invasion. , Iino Y; Yokoe T; Maemura M; Horiguchi J; Takei H; Ohwada S; Morishita Y ,Second Department of Surgery, Gunma University School of Medicine, Japan. ,Anticancer Res, 15(6B):2907-11 1995 Nov-Dec.

In vitro reactivity to a protein-bound polysaccharide PSK of peripheral blood lymphocytes from patients with gastrointestinal cancer. The effect of PSK, a protein-bound polysaccharide and an immunomodulator, on lymphocytes was examined in vitro for 36 patients with gastric cancer and 26 with colorectal cancer. Cultured lymphocytes with PSK at 100 micrograms/ml increased the level of DNA synthesis, as determined by the 3H-thymidine uptake, from 0.9 to 3.0 fold, compared to the PSK non-treated cells. The increase was 1.36 +/- 0.46 fold for the gastric cancer cases and 1.37 + 0.45 fold for the colorectal cancer cases, and these levels were significantly the finding of 1.93 + 0.55 fold for a control group consisting of 15 healthy volunteers (P < 0.01). When the 1.3 fold increase of 3H-thymidine uptake was defined as the PSK-reactive group, 52.8% (19/36) of the patients with gastric cancer and 50.0% (13/26) for colorectal cancer were found in the PSK-reactive group. The PSK-reactive group demonstrated no relation to the age and sex of the patients, tissue differentiation type or tumor advancement. Our findings thus show that the in vitro activation of lymphocytes by PSK can help identify the candidates with either gastric or colorectal cancer who are the best suited to undergo immunochemotherapy including treatment with PSK.,Sugimachi K; Maehara Y; Kusumoto T; Okamura T; Korenaga D; Kohnoe S; Baba H; Anai H ,Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan. ,Anticancer Res, 15(5B):2175-9 1995 Sep-Oct

Prolongation of the survival period with the biological response modifier PSK in rats bearing N-methyl-N-nitrosourea-induced mammary gland tumors. , The antitumor effects of a protein-bound polysaccharide (PSK) obtained from cultured mycelia of Coriolus versicolor in basidiomycetes on mammary gland tumors produced in Sprague-Dawley rats by the intravenous injection of N-methyl-N-nitrosourea were investigated. PSK prolonged the survival period of tumor-bearing rats significantly, when given at the dose of 250 mg/kg twice a week for 3 weeks after the tumor reached 100 mm2 in size (p = 0.011 by log rank test and p = 0.023 by generalized Wilcoxon test). These findings suggest that PSK is effective in the prolongation of the survival period in the rat autochthonous tumor model, acting at the growth stage of the tumor during carcinogenesis. Fujii T; Saito K; Matsunaga K; Oguchi Y; Ikuzawa M; Furusho T; Taguchi T ,Kureha Chemical Ind. Co., Ltd., Biomedical Research Laboratories, Tokyo, Japan. ,In Vivo, 9(1):55-7 1995 Jan-Feb

Polysaccharide peptide (PSP) restores immunosuppression induced by cyclophosphamide in rats., Polysaccharide peptide (PSP) is a protein-bound polysaccharide extracted from an edible mushroom, Coriolus versicolor. Effects of PSP (2g/kg/day) on cyclophosphamide (CPA, 40 mg/kg/2 days)-induced immunosuppression were investigated by determining lymphocyte proliferation, Natural killer (NK) cell formation, IgG and IL-2 concentration, WBC count and the weight of organs after rats were treated with or without CPA in the presence or absence of PSP. The results demonstrated that PSP possessed immunopotentiating effect, being effective in restoring CPA-induced immunosuppression such as depressed lymphocyte proliferation, Natural Killer cell function, production on white blood cell and the growth of spleen and thymus in rats as well as in increasing both IgG and IL-2 production on which CPA did not have significant effects under the conditions of our experiments. PSP can partly restore CPA-induced immunosuppression. Based on our findings and the data accumulated so far, it was suggested that PSP should be considered as an useful adjuvant especially combined with CPA or other chemotherapy in clinical treatment of cancer patients. The mechanism by which PSP restores the immunosuppression induced by CPA is unclear. ,Qian ZM; Xu MF; Tang PL ,Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong. , Am J Chin Med, 25(1):27-35 1997

Effect of polysaccharide peptide (PSP) on in vivo sulphation and glucuronidation of paracetamol in the rat. , The effect of polysaccharide peptide (PSP), an immunomodulator isolated from Coriolus versicolor COV-1, on the disposition of paracetamol was investigated in the rat. PSP (100 and 200 mg/kg, i.v.) was administered 30 min before a moderate dose (100 mg/kg, i.v.) of paracetamol was given. Plasma and bile concentrations of paracetamol, paracetamol glucuronide and paracetamol sulphate were measured by high performance liquid chromatography. The pharmacokinetics of paracetamol (100 mg/kg) alone was consistent with those reported previously, using a one-compartment model. PSP (200 mg/kg) significantly (P < 0.05) increased the clearance (controls, 19.06 +/- 2.74 ml/min/kg: PSP treated, 26.22 +/- 0.84 ml/min/kg) and volume of distribution (controls, 1.35 +/- 0.11 l/kg: PSP treated, 1.61 +/- 0.04 l/kg) of paracetamol by 37% and 21%, respectively. These changes were associated with concomitant increases in the glucuronide and sulphate metabolites in plasma, with significant increases in the Cmax and Tmax for both metabolites. The biliary excretion rate of paracetamol glucuronide and paracetamol sulphate were also measured. The Cmax values of paracetamol sulphate were significantly (P < 0.01) increased by 2.4-fold from 907.8 +/- 157.7 micrograms/ml (controls) to 3061 +/- 331 micrograms/ml after PSP treatment. The lower dose of PSP (100 mg/kg) had no significant effect on the disposition of paracetamol in this study, which agreed with previous reports that a low dose of PSP (100-200 mg/kg, i.p.) was less effective in the protection against paracetamol-induced hepatotoxicity. The time course of the increase in paracetamol sulphate in plasma and bile in this study coincided with the transient perturbation of glutathione (GSH) turnover by a similar dose range of PSP previously described, such that more cysteine was available for oxidation to inorganic sulphate. This increase in sulphate conjugation by PSP would, in part, contribute to the increase in disposition of paracetamol and may be related to the ability of PSP to decrease the covalent binding of paracetamol to microsomal proteins previously reported. Further studies are necessary to understand the mechanism(s) involved in the PSP-induced increases in paracetamol glucuronide and paracetamol sulphate formation and biliary excretion. , Yeung JH; Chiu LC; Ooi VE ,Department of Pharmacology, Chinese University of Hong Kong, Shatin. , Eur J Drug Metab Pharmacokinet, 20(4):287-92 1995 Oct-Dec

Effect of polysaccharide-peptide (PSP), an extract from yun-zhi, on chemotherapy-induced cytopenias. , Polysaccharide-peptide (PSP) is a protein-bound complex carbohydrate derived from mycelia extract of Chinese fungus coriolus versicolor, or better known as Yun-Zhi. It has been shown to inhibit growth of cultured tumour cells, and it prevents cytotoxic-induced bone marrow suppression. An animal study was conducted with 24 Wistar rats to verify the myeloprotective effect of PSP. The rats were divided into two equal groups: group A (given cyclophosphamide [CTX]) and group B (given PSP and CTX). The body weights were similar in both groups of rats. In phase 1, all rats were given intravenous CTX 75 mg/kg. In addition, B rats received PSP 20 mg/day orally from 7 days before CTX to 14 days after CTX. Phase 2 was carried out two weeks after full recovery from CTX-induced cytopenia. The CTX was decreased to 60 mg/kg, and the group B rats received an increased dose of PSP 1.2 g/day for the same 21 days. In both phases, the CTX was well tolerated. Nadir white blood cell count was reached on day 4 and all counts recovered by day 10. There was no difference in absolute neutrophil, lymphocyte and platelet counts between groups A and B. We concluded that oral PSP did not prevent CTX-induced cytopenia in rats.,Zhou LQ; Koo WH; Ang PT ,Department of Medical Oncology, Singapore General Hospital, Singapore. ,Ann Acad Med Singapore, 25(1):143-6 1996 Jan

Pancreatic spasmolytic polypeptide protects the gastric mucosa but does not inhibit acid secretion or motility. , The objectives of these studies were to examine whether the trefoil peptide porcine pancreatic spasmolytic polypeptide (PSP) had gastric mucosal protectant properties similar to its human equivalent human spasmolytic polypeptide (hSP) and to confirm the antisecretory and antimotility action of the peptide. PSP and recombinant hSP reduced gastric mucosal damage caused by a combination of subcutaneous indomethacin and restraint stress in the conscious rat. At a dose of 500 micrograms/kg bolus plus 500 micrograms.kg-1.h-1 sc, PSP significantly reduced the total area of damage by 58%. PSP at a dose of 150 micrograms/kg iv had no inhibitory effect on pentagastrin-stimulated gastric acid secretion in the perfused stomachs of anesthetized rats. This lack of antisecretory activity was confirmed in vitro using an isolated stomach preparation from the immature rat. PSP and hSP at concentrations up to 800 nM did not inhibit electrically or chemically evoked contractions of the guinea pig ileum and duodenum in vitro. Thus antisecretory and antimotility actions do not underlie the mucosal protectant properties of PSP. PSP did, however, stimulate cell migration, and this may, at least in part, account for its protectant properties. , McKenzie C; Marchbank T; Playford RJ; Otto W; Thim L; Parsons ME , Gastrointestinal Pharmacology Unit, University of Hertfordshire, Hatfield, United Kingdom. ,Am J Physiol, 273(1 Pt 1):G112-7 1997 July.

Effect of polysaccharide peptide (PSP) on in vivo sulphation and glucuronidation of paracetamol in the rat. , The effect of polysaccharide peptide (PSP), an immunomodulator isolated from Coriolus versicolor COV-1, on the disposition of paracetamol was investigated in the rat. PSP (100 and 200 mg/kg, i.v.) was administered 30 min before a moderate dose (100 mg/kg, i.v.) of paracetamol was given. Plasma and bile concentrations of paracetamol, paracetamol glucuronide and paracetamol sulphate were measured by high performance liquid chromatography. The pharmacokinetics of paracetamol (100 mg/kg) alone was consistent with those reported previously, using a one-compartment model. PSP (200 mg/kg) significantly (P < 0.05) increased the clearance (controls, 19.06 +/- 2.74 ml/min/kg: PSP treated, 26.22 +/- 0.84 ml/min/kg) and volume of distribution (controls, 1.35 +/- 0.11 l/kg: PSP treated, 1.61 +/- 0.04 l/kg) of paracetamol by 37% and 21%, respectively. These changes were associated with concomitant increases in the glucuronide and sulphate metabolites in plasma, with significant increases in the Cmax and Tmax for both metabolites. The biliary excretion rate of paracetamol glucuronide and paracetamol sulphate were also measured. The Cmax values of paracetamol sulphate were significantly (P < 0.01) increased by 2.4-fold from 907.8 +/- 157.7 micrograms/ml (controls) to 3061 +/- 331 micrograms/ml after PSP treatment. The lower dose of PSP (100 mg/kg) had no significant effect on the disposition of paracetamol in this study, which agreed with previous reports that a low dose of PSP (100-200 mg/kg, i.p.) was less effective in the protection against paracetamol-induced hepatotoxicity. The time course of the increase in paracetamol sulphate in plasma and bile in this study coincided with the transient perturbation of glutathione (GSH) turnover by a similar dose range of PSP previously described, such that more cysteine was available for oxidation to inorganic sulphate. This increase in sulphate conjugation by PSP would, in part, contribute to the increase in disposition of paracetamol and may be related to the ability of PSP to decrease the covalent binding of paracetamol to microsomal proteins previously reported. Further studies are necessary to understand the mechanism(s) involved in the PSP-induced increases in paracetamol glucuronide and paracetamol sulphate formation and biliary excretion. , Yeung JH; Chiu LC; Ooi VE , Department of Pharmacology, Chinese University of Hong Kong, Shatin. , Eur J Drug Metab Pharmacokinet, 20(4):287-92 1995 Oct-Dec

A review of research on the protein-bound polysaccharide (polysaccharopeptide, PSP) from the mushroom Coriolus versicolor (Basidiomycetes: Polyporaceae)., 1. Protein-bound polysaccharides, designated as PSK and PSP, have been isolated from the CM-101 strain and the COV-1 strain, respectively, of the mushroom Coriolus versicolor. This article aims at summarizing existing research findings about PSP since information on PSK is well documented. 2. PSP possesses a molecular weight of approximately 100 kDa. Glutamic and aspartic acids are abundant in its polypeptide component, whereas its polysaccharide component is made up of monosaccharides with alpha-1,4 and beta-1,3 glucosidic linkages. The presence of fucose in PSK and rhamnose and arabinose in PSP distinguishes the two protein-bound polysaccharides, which are otherwise chemically similar. 3. PSP is classified as a biological response modifier. It induces, in experimental animals, increased gamma-interferon production, interleukin-2 production, and T-cell proliferation. It also counteracts the depressive effect of cyclophosphamide on white blood cell count, interleukin-2 production and delayed-type hypersensitivity reaction. Its antiproliferative activity against tumor cell lines and in vivo antitumor activity have been demonstrated. A small peptide with a molecular weight of 16-18 kDa originating from PSP has been produced with antiproliferative and antitumor activities. 4. PSP administered to patients with esophageal cancer, gastric cancer and lung cancer, and who are undergoing radiotherapy or chemotherapy, helps alleviate symptoms and prevents the decline in immune status. ,Ng TB , Department of Biochemistry, Faculty of Medicine, Chinese University of Hong Kong, Shatin, N.T., Hong Kong. ,Gen Pharmacol, 30(1):1-4 1998 Jan

Antitumor effects of a refined polysaccharide peptide fraction isolated from Coriolus versicolor: in vitro and in vivo studies. , RPSP, a refined polysaccharide peptide fraction isolated by fast performance liquid chromatography (FPLC) from the crude powder of total peptide-bound polysaccharides of cultivated Coriolus versicolor Cov-1 dose-dependently inhibited the proliferation of a human hepatoma cell line (HEPG2). The effective dose causing 50% inhibition following 3-day exposure to RPSP was 243 +/- 36 micrograms/ml for HEPG2. However, little or no inhibitory effects were detected in normal human foetal hepatocytes. On the other hand, in the pretreatment group, in which RPSP was administered i.p. for two weeks before sarcoma 180 inoculation in nude mice, the incidence of tumor growth was less (2 out of 5 mice) than that of the control group (all 5 mice). The tumor size of the control group was about 3-5 times bigger than that of the pretreatment group. In tumor-bearing nude mice, 5 days after sarcoma 180 inoculation, i.v. administration of RPSP significantly suppressed the growth of tumor mass. The inhibition rate was 93.6% on day 13. Furthermore, administration of RPSP did not cause any pathological lesions in vital organs of rabbits such as heart, liver, spleen, lung and kidney. In conclusion, these results indicate that RPSP acts by directly suppressing tumor cell growth in vitro and the prevention of in vivo growth of tumor mass is probably mediated also via its immunomodulating effects., Dong Y; Kwan CY; Chen ZN; Yang MM , Department of Physiology, Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong. , Res Commun Mol Pathol Pharmacol, 92(2):140-8 1996 May .

Polysaccharide-peptide complexes from the cultured mycelia of the mushroom Coriolus versicolor and their culture medium activate mouse lymphocytes and macrophages.  The aim of this study was to investigate the effects of the mushroom Coriolus versicolor on cells of the immune system. The cultured mycelia of the mushroom Coriolus versicolor and their culture medium were separately extracted with boiling water. The resulting polysaccharopeptide preparations were designated intramycelial (IM) and extramycelial materials (EM), and were separated by gel filtration before determining their effects on lymphocytes and macrophages in vitro and in vivo. After gel filtration on Sepharose 6B, only a single peak with a molecular weight of 13-19 KDa was obtained. Gel filtration of IM and EM on Sephadex G-50 revealed the presence of a larger peak of 28 KDa (from IM) and 15 KDa (from EM) and a smaller peak of 3.5 KDa. IM, EM and their large molecular peaks enhanced the mitogenic response of T-cells from BALB/c mice in vitro. Splenocytes from C57BL/6 mice pre-treated by force-feeding with IM and EM demonstrated an augmented mitogenic response to Con A. The macrophages of C57BL/6 mice that had been pre-treated with IM or EM showed an enhanced production of nitrite ions. The results indicate that both mouse lymphocytes and macrophages were activated by preparations of polysaccharopeptide from cultured mycelia and culture medium of C. versicolor. However, no direct cytotoxic activity against fibroblasts, hepatoma cells and choriocarcinoma cells could be demonstrated. , Wang HX; NG TB; Liu WK; Ooi VE; Chang ST , Department of Biology, Chinese University of Hong Kong, Shatin, Hong Kong. , Int J Biochem Cell Biol, 28(5):601-7 1996 May

Effect of polysaccharide-peptide (PSP), an extract from yun-zhi, on chemotherapy-induced cytopenias., Polysaccharide-peptide (PSP) is a protein-bound complex carbohydrate derived from mycelia extract of Chinese fungus coriolus versicolor, or better known as Yun-Zhi. It has been shown to inhibit growth of cultured tumour cells, and it prevents cytotoxic-induced bone marrow suppression. An animal study was conducted with 24 Wistar rats to verify the myeloprotective effect of PSP. The rats were divided into two equal groups: group A (given cyclophosphamide [CTX]) and group B (given PSP and CTX). The body weights were similar in both groups of rats. In phase 1, all rats were given intravenous CTX 75 mg/kg. In addition, B rats received PSP 20 mg/day orally from 7 days before CTX to 14 days after CTX. Phase 2 was carried out two weeks after full recovery from CTX-induced cytopenia. The CTX was decreased to 60 mg/kg, and the group B rats received an increased dose of PSP 1.2 g/day for the same 21 days. In both phases, the CTX was well tolerated. Nadir white blood cell count was reached on day 4 and all counts recovered by day 10. There was no difference in absolute neutrophil, lymphocyte and platelet counts between groups A and B. We concluded that oral PSP did not prevent CTX-induced cytopenia in rats. , Zhou LQ; Koo WH; Ang P T ,Department of Medical Oncology, Singapore General Hospital, Singapore. ,Ann Acad Med Singapore, 25(1):143-6 1996 Jan

Polysaccharopeptide from the mushroom Coriolus versicolor possesses analgesic activity but does not produce adverse effects on female reproductive or embryonic development in mice. , 1. Coriolus versicolor polysaccharopeptide has been reported to exert immunomodulatory and antitumor actions. The present study showed that it exhibits analgesic activity in the hot-plate test upon intraperitoneal administration to ICR mice. 2. It did not affect ovarian steroidogenesis, ovulation and midterm gestation in mice. It did not exert an adverse effect on mouse embryonic development either, as evidenced by the lack of an effect on somite number, axial length and the incidence of abnormalities in heartbeat, yolk sac circulation, optic vesicle, otic vesicle, shape of body axis, forelimb buds, branchial apparatus, cranial neural tube and head size. 3. Its analgesic activity would add to its attribute as an immunomodulatory and antitumor drug. ,Ng TB; Chan WY , Departments of Biochemistry and Anatomy, Faculty of Medicine, Chinese University of Hong Kong, Shatin, N.T., Hong Kong. ,Gen Pharmacol, 29(2):269-73 1997 Aug .

Polysaccharide peptide (PSP) restores immunosuppression induced by cyclophosphamide in rats. Polysaccharide peptide (PSP) is a protein-bound polysaccharide extracted from an edible mushroom, Coriolus versicolor. Effects of PSP (2g/kg/day) on cyclophosphamide (CPA, 40 mg/kg/2 days)-induced immunosuppression were investigated by determining lymphocyte proliferation, atural killer (NK) cell formation, IgG and IL-2 concentration, WBC count and the weight of organs after rats were treated with or without CPA in the presence or absence of PSP. The results demonstrated that PSP possessed immunopotentiating effect, being effective in restoring CPA-induced immunosuppression such as depressed lymphocyte proliferation, Natural Killer cell function, production on white blood cell and the growth of spleen and thymus in rats as well as in increasing both IgG and IL-2 production on which CPA did not have significant effects under the conditions of our experiments. PSP can partly restore CPA-induced immunosuppression. Based on our findings and the data accumulated so far, it was suggested that PSP should be considered as an useful adjuvant especially combined with CPA or other chemotherapy in clinical treatment of cancer patients. The mechanism by which PSP restores the immunosuppression induced by CPA is unclear. Qian ZM; Xu MF; Tang PL , Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong. ,Am J Chin Med, 25(1):27-35 1997

Polysaccharopeptide from Coriolus versicolor has potential for use against human immunodeficiency virus type 1 infection., Polysaccharopeptide (PSP) isolated from the edible mushroom Coriolus versicolor was tested for its potential as an anti-human immunodeficiency virus type 1 (HIV-1) compound in a series of in vitro assays. It demonstrated inhibition of the interaction between HIV-1 gp 120 and immobilized CD4 receptor (IC50 = 150 microg/ml), potent inhibition of recombinant HIV-1 reverse transcriptase (IC50 = 6.25 microg/ml), and inhibited a glycohydrolase enzyme associated with viral glycosylation. These properties, coupled with its high solubility in water, heat-stability and low cytotoxicity, make it a useful compound for further studies on its possible use as an anti-viral agent in vivo. Collins RA; Ng TB ,Department of Biochemistry, The Chinese University of Hong Kong, Shatin, New Territories. racollins@cuhk.edu.hk ,Life Sci, 60(25):PL383-7 1997

References:

• Wae and T.F. Liu, Clinical Experience in the Use of PSP ,Cancer hospital, Shanghai Medical University

• Z.Y. Sun et al, The Preliminary Appraisal of Polysaccharide Peptide (PSP) in Malignant and Non-malignant Disease, Shanghai Medical University.

• Fujii, T., Kano, T., Saito, K. Kobayasi, Y., Iijima, H., Matsumoto, T., Yoshikumi, C. and Taguchi, T. (1987) Effect of PSK on prohibited immunity of splenectomized mice. Anticancer Res. 7,845.

• Hayakawa K, Mitshuhashi N. Saito Y, et al. Effect of Krestin (PSK) as adjuvant treatment on the prognosis after radical radiotherapy in patients with non-small cell lung cancer. Anticancer Res. 13:1815-20, 1993.

• Iino Y. Yokoe T, Ohwada S, et al. Eight-year results of adjuvant immunochemotherapies vs. chemotherapy in the treatment of operable breast cancer. 18th International Congress of Chemotherapy. June 27-July 2, 1993. Stockholm, Sweden, P. 162 1993.

• Li, X.M. and Xu, L.Z. (1987)A study of anticancer effects of PSP and PSK on human tumor cell lines in vitro. Acto Acad. Med. Shanghai 14,23.

• Shiu, W.C.T., Leung, T.W.T. and Tao, M. (1992) A Clinical study of PSP on peripheral blood counts during chemotherapy. Phytotherapy Res. 6, 217.

• Yang,M.M.P., Chen, Z. and Kwok J.s.l. (1992b) The antitumor effect of a small polypeptide from Coriolus versicolor. Amer. J. Chin. Med. 20,221.

• Yang, Q.Y. and Yuan, P. (1986) Isolation of the polysaccharide components of PSP. J. Shanghai Tech. Univ. 4, 36.

• You, J.s., Hau, D.M., Chen, K.T. and Huang, H.F. (1994) Combined effects of chuling (Polyporus umbellatus) extract and mitomycin C on experimental liver cancer. Amer. J. Chin. Med. 22, 19.

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Cordyceps sinensis

Ganoderma lucidum